Wellcome Trust Centre for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, UK.
Eur Respir J. 2010 May;35(5):1106-12. doi: 10.1183/09031936.00087009. Epub 2009 Sep 24.
Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.
Gc 蛋白是维生素 D 结合蛋白的一种，其各亚型在与维生素 D 代谢物结合方面存在差异，而后者又可调节抗分枝杆菌免疫。我们进行了相关研究，以确定 Gc 基因型是否与结核病（TB）易感性相关。在英国、巴西和南非，我们分别招募了以下人群进行病例对照研究：英国招募了 123 例成年 TB 患者和 140 例对照者，均为古吉拉特裔亚洲人；巴西招募了 130 例成年 TB 患者和 78 例对照者；南非招募了 281 例儿童 TB 患者和 182 例对照者。我们确定了 Gc 基因型，并比较了病例组和对照组之间的 Gc 基因型频率。我们还对 139 例古吉拉特裔亚洲人进行了回顾性血清 25-羟维生素 D（25(OH)D）浓度检测，并按维生素 D 状态对病例对照分析进行了分层。我们还对 36 例古吉拉特裔亚洲人 TB 接触者进行了干扰素（IFN）-γ释放试验。与 Gc1/1 基因型相比，Gc2/2 基因型与古吉拉特裔亚洲人活动性 TB 的易感性密切相关（比值比 2.81，95%置信区间 1.19-6.66；p = 0.009）。如果血清 25(OH)D <20 nmol·L(-1)（p = 0.01），则这种关联得以保留；如果血清 25(OH)D > =20 nmol·L(-1)（p = 0.36），则这种关联则不会保留。古吉拉特裔亚洲人 TB 接触者中，Gc2 等位基因的携带与结核菌素刺激 IFN-γ释放的 PPD 增加有关（p = 0.02）。在其他研究的种族群体中，未观察到 Gc 基因型与 TB 易感性之间存在关联。
